title: Knockout of striatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation.
abstract: STriatal Enriched protein tyrosine Phosphatase (STEP) is a brain-specific protein that is thought to play a role in synaptic plasticity. This hypothesis is based on previous findings demonstrating a role for STEP in the regulation of the extracellular signal-regulated kinase1/2 (ERK1/2). We have now generated a STEP knockout mouse and investigated the effect of knocking out STEP in the regulation of ERK1/2 activity. Here, we show that the STEP knockout mice are viable and fertile and have no detectable cytoarchitectural abnormalities in the brain. The homozygous knockout mice lack the expression of all STEP isoforms, whereas the heterozygous mice have reduced STEP protein levels when compared with the wild-type mice. The STEP knockout mice show enhanced phosphorylation of ERK1/2 in the striatum, CA2 region of the hippocampus, as well as central and lateral nuclei of the amygdala. In addition, the cultured neurons from KO mice showed significantly higher levels of pERK1/2 following synaptic stimulation when compared with wild-type controls. These data demonstrate more conclusively the role of STEP in the regulation of ERK1/2 activity.
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Deepa V
authors.initials: DV
authors.lastname: Venkitaramani
authors.forename: Surojit
authors.initials: S
authors.lastname: Paul
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kurup
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Lyal
authors.initials: L
authors.lastname: Tressler
authors.forename: Melanie
authors.initials: M
authors.lastname: Allen
authors.forename: Rosalba
authors.initials: R
authors.lastname: Sacca
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lombroso
mesh_terms: D000679:Amygdala / Q000201:enzymology; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C082101:Ptpn5 protein, mouse